The oral and gut microbiotas are distinct microbial communities with unique compositions and functions but they can communicate and influence each other. Antibiotics disrupt the oral and gut ecosystems, leading to dysbiosis and increased gut epithelial permeability. Nitrate may promote inter-kingdom crosstalk during dysbiosis by either generating redox signalling species or serving as a substrate for bacteria in both ecosystems.

Nitrate may act as a regulator of ^•NO bioavailability via sequential reduction along the nitrate-nitrite-NO pathway with widespread health benefits, including a eubiotic effect on the oral and gut microbiota. Here, we discuss the molecular mechanisms of microbiota-host communication through redox pathways, via the production of ^•NO and oxidants by the family of NADPH oxidases, namely hydrogen peroxide (via Duox2), superoxide radical (via Nox1 and Nox2) and peroxynitrite, which leads to downstream activation of stress responses (Nrf2 and NFkB pathways) in the host mucosa. The activation of Nox2 by microbial metabolites is also discussed. Finally, we propose a new perspective in which both oral and gut microbiota communicate through redox pathways, with nitrate as the pivot linking both ecosystems.

Cyclic nucleotides serve as second messengers throughout kingdoms of life and regulate various pathways. Here, we review recent milestones in cyclic nucleotide biology, focusing on different enzyme folds that synthesize these signals, their regulatory mechanisms, and pleiotropic downstream signaling events. Our particular focus is on enzyme-centered approaches specifically targeting nucleotidyltransferases, which have enabled the discovery of novel cyclic nucleotides.

Cyclic nucleotides are the most diversified category of second messengers and are found in all organisms modulating diverse pathways. While cAMP and cGMP have been studied over 50 years, cyclic di-nucleotide signaling in eukaryotes emerged only recently with the anti-viral molecule 2´3´cGAMP. Recent breakthrough discoveries have revealed not only the astonishing chemical diversity of cyclic nucleotides but also surprisingly deep-rooted evolutionary origins of cyclic oligo-nucleotide signaling pathways and structural conservation of the proteins involved in their synthesis and signaling. Here we discuss how enzyme-centered approaches have paved the way for the identification of several cyclic nucleotide signals, focusing on the advantages and challenges associated with deciphering the activation mechanisms of such enzymes.

Metabolic homeostasis depends on the functional remodeling of organelles. During starvation, this is especially evident for mitochondria. In this perspective, we outline a possible mechanism by which lipid transport at membrane contact sites might control the adaptation of mitochondrial activities. We conclude with the notion that mitochondria interact with a whole network of organelles to achieve this important physiological task.

Organelles form physical and functional contact between each other to exchange information, metabolic intermediates, and signaling molecules. Tethering factors and contact site complexes bring partnering organelles into close spatial proximity to establish membrane contact sites (MCSs), which specialize in unique functions like lipid transport or Ca²⁺ signaling. Here, we discuss how MCSs form dynamic platforms that are important for lipid metabolism. We provide a perspective on how import of specific lipids from the ER and other organelles may contribute to remodeling of mitochondria during nutrient starvation. We speculate that mitochondrial adaptation is achieved by connecting several compartments into a highly dynamic organelle network. The lipid droplet appears to be a central hub in coordinating the function of these organelle neighborhoods.

Certain eukaryotes can synthesize triacylglycerol using an acyl-CoA-independent pathway. This activity is mediated by phospholipid diacylglycerol acyl transferases that use fatty acids from phospholipids as acyl donors. In this perspective, we review the current knowledge on these enzymes and propose that local modulation of phospholipids mediated by this pathway impacts the function and morphology of the targeted organelle.

Triglycerides constitute an inert storage form for fatty acids deposited in lipid droplets and are mobilized to provide metabolic energy or membrane building blocks. The biosynthesis of triglycerides is highly conserved within eukaryotes and normally involves the sequential esterification of activated fatty acids with a glycerol backbone. Some eukaryotes, however, can also use cellular membrane lipids as direct fatty acid donors for triglyceride synthesis. The biological significance of a pathway that generates triglycerides at the expense of organelle membranes has remained elusive. Here we review current knowledge on how cells use membrane lipids as fatty acid donors for triglyceride synthesis and discuss the hypothesis that a primary function of this pathway is to regulate membrane lipid remodeling and organelle function.

The nuclear pore complex is a large multiprotein complex traversing the nuclear envelope. Many of its components harbor intrinsically disordered regions that undergo spontaneous condensation. Here, we discuss how assembly factors may guide their condensation, which must be carefully coordinated in space and time. We further discuss how defects in this process contribute to human pathologies, focusing on neurological disorders.

The nuclear pore complex (NPC) is among the most elaborate protein complexes in eukaryotes. While ribosomes and proteasomes are known to require dedicated assembly machinery, our understanding of NPC assembly is at a relatively early stage. Defects in NPC assembly or homeostasis are tied to movement disorders, including dystonia and amyotrophic lateral sclerosis (ALS), as well as aging, requiring a better understanding of these processes to enable therapeutic intervention. Here, we discuss recent progress in the understanding of NPC assembly and highlight how related defects in human disorders can shed light on NPC biogenesis. We propose that the condensation of phenylalanine-glycine repeat nucleoporins needs to be carefully controlled during NPC assembly to prevent aberrant condensation, aggregation, or amyloid formation.